Digital Commons Network^™

It Is Better To Light A Candle Than To Curse The Darkness: Single-Cell Transcriptomics Sheds New Light On Pancreas Biology And Disease, Amelia T Cephas, William L Hwang, Anirban Maitra, Oren Parnas, Kathleen E Delgiorno

Faculty, Staff and Student Publications

Recent advances in single-cell RNA sequencing and bioinformatics have drastically increased our ability to interrogate the cellular composition of traditionally difficult to study organs, such as the pancreas. With the advent of these technologies and approaches, the field has grown, in just a few years, from profiling pancreas disease states to identifying molecular mechanisms of therapy resistance in pancreatic ductal adenocarcinoma, a particularly deadly cancer. Single-cell transcriptomics and related spatial approaches have identified previously undescribed epithelial and stromal cell types and states, how these populations change with disease progression, and potential mechanisms of action which will serve as the basis …

Pan-Cancer T Cell Atlas Links A Cellular Stress Response State To Immunotherapy Resistance, Yanshuo Chu, Enyu Dai, Yating Li, Guangchun Han, Guangsheng Pei, Davis R Ingram, Krupa Thakkar, Jiang-Jiang Qin, Minghao Dang, Xiuning Le, Can Hu, Qing Deng, Ansam Sinjab, Pravesh Gupta, Ruiping Wang, Dapeng Hao, Fuduan Peng, Xinmiao Yan, Yunhe Liu, Shumei Song, Shaojun Zhang, John V Heymach, Alexandre Reuben, Yasir Y Elamin, Melissa P Pizzi, Yang Lu, Rossana Lazcano, Jian Hu, Mingyao Li, Michael Curran, Andrew Futreal, Anirban Maitra, Amir A Jazaeri, Jaffer A Ajani, Charles Swanton, Xiang-Dong Cheng, Hussein A Abbas, Maura Gillison, Krishna Bhat, Alexander J Lazar, Michael Green, Kevin Litchfield, Humam Kadara, Cassian Yee, Linghua Wang

Faculty, Staff and Student Publications

Tumor-infiltrating T cells offer a promising avenue for cancer treatment, yet their states remain to be fully characterized. Here we present a single-cell atlas of T cells from 308,048 transcriptomes across 16 cancer types, uncovering previously undescribed T cell states and heterogeneous subpopulations of follicular helper, regulatory and proliferative T cells. We identified a unique stress response state, TSTR, characterized by heat shock gene expression. TSTR cells are detectable in situ in the tumor microenvironment across various cancer types, mostly within lymphocyte aggregates or potential tertiary lymphoid structures in tumor beds or surrounding tumor edges. T cell states/compositions correlated with …

Long-Term Outcomes Of Bevacizumab And Chemoradiation For Locoregionally Advanced Nasopharyngeal Carcinoma: A Nonrandomized Controlled Trial, Nancy Y Lee, Jonathan Harris, John Kim, Adam Garden, James Mechalakos, David G Pfister, Anthony T C Chan, Kenneth Hu, A Dimitrios Colevas, Steven Frank, George Shenouda, Voichita Bar-Ad, John N Waldron, Paul M Harari, Adam Raben, Pedro Torres-Saavedra, Quynh-Thu Le

Faculty, Staff and Student Publications

Importance: The long-term outcomes associated with adding bevacizumab, a vascular endothelial growth factor inhibitor, to standard chemoradiation have continued to be favorable for a group of patients with locoregionally advanced nasopharyngeal carcinoma (NPC).

Objective: To assess long-term toxic effects and clinical outcomes associated with chemotherapy, radiation therapy (RT), and bevacizumab for NPC.

Design, setting, and participants: This single-arm phase II nonrandomized controlled trial was conducted by the National Cancer Trials Network group and NRG Oncology (formerly Radiation Therapy Oncology Group), with accrual from December 13, 2006, to February 5, 2009, and data analysis from June 26 to July 1, 2019. …

A Virtual Audit System For Intensity-Modulated Radiation Therapy Credentialing In Japan Clinical Oncology Group Clinical Trials: A Pilot Study, Mitsuhiro Nakamura, Dejun Zhou, Toshiyuki Minemura, Satoshi Kito, Hiroyuki Okamoto, Naoki Tohyama, Masahiko Kurooka, Yu Kumazaki, Masayori Ishikawa, Catharine H Clark, Elizabeth Miles, Joerg Lehmann, Nicolaus Andratschke, Stephen Kry, Satoshi Ishikura, Takashi Mizowaki, Teiji Nishio

Faculty, Staff and Student Publications

Purpose: The Medical Physics Working Group of the Radiation Therapy Study Group at the Japan Clinical Oncology Group is currently developing a virtual audit system for intensity-modulated radiation therapy dosimetry credentialing. The target dosimeters include films and array detectors, such as ArcCHECK (Sun Nuclear Corporation, Melbourne, Florida, USA) and Delta4 (ScandiDos, Uppsala, Sweden). This pilot study investigated the feasibility of our virtual audit system using previously acquired data.

Methods: We analyzed 46 films (32 and 14 in the axial and coronal planes, respectively) from 29 institutions. Global gamma analysis between measured and planned dose distributions used the following settings: 3%/3 …

Irf7 And Unc93b1 Variants In An Infant With Recurrent Herpes Simplex Virus Infection., Megan H. Tucker, Wei Yu, Heather Menden, Sheng Xia, Carl F. Schreck, Margaret Gibson, Daniel A. Louiselle, T Pastinen, Nikita Raje, Venkatesh Sampath

Manuscripts, Articles, Book Chapters and Other Papers

Neonatal herpes simplex virus (HSV) infection is a devastating disease with substantial morbidity and mortality. The genetic basis of susceptibility to HSV in neonates remains undefined. We evaluated a male infant with neonatal skin/eye/mouth (SEM) HSV-1 disease, who had complete recovery after acyclovir but developed HSV-1 encephalitis at 1 year of age. An immune workup showed an anergic PBMC cytokine response to TLR3 stimulation but no other TLRs. Exome sequencing identified rare missense variants in IFN-regulatory factor 7 (IRF7) and UNC-93 homolog B1 (UNC93B1). PBMC single-cell RNA-Seq done during childhood revealed decreased expression of several innate immune genes and a …

Recruitment And Reach In A School-Based Pediatric Obesity Intervention Trial In Rural Areas., Bethany Forseth, Brittany Lancaster, Megan Olalde, Christie A. Befort, Rebecca E. Swinburne Romine, Meredith Dreyer, Kelsey Dean, Eve-Lynn Nelson, Ann M. Davis

Manuscripts, Articles, Book Chapters and Other Papers

INTRODUCTION: The purpose of this study is to evaluate two recruitment strategies on schools and participant participation rates and representativeness (reach) within a pediatric obesity treatment trial tailored for families who live in rural areas.

METHODS: Recruitment of schools was evaluated based on their progress toward enrolling participants. Recruitment and reach of participants were evaluated using (1) participation rates and (2) representativeness of demographics and weight status of participants compared to eligible participants (who did not consent and enroll) and all students (regardless of eligibility). School recruitment, as well as participant recruitment and reach, were evaluated across recruitment methods comparing …

Flt3 Inhibitors Upregulate Cxcr4 And E-Selectin Ligands Via Erk Suppression In Aml Cells And Cxcr4/E-Selectin Inhibition Enhances Anti-Leukemia Efficacy Of Flt3-Targeted Therapy In Aml, Yannan Jia, Weiguo Zhang, Mahesh Basyal, Kyung Hee Chang, Lauren Ostermann, Jared K Burks, Charlie Ly, Hong Mu-Mosley, Qi Zhang, Xin Han, William E Fogler, John L Magnani, Arnaud Lesegretain, Anna A Zal, Tomasz Zal, Michael Andreeff

Faculty, Staff and Student Publications

No abstract provided.

A Role For Protein Arginine Methyltransferase 7 In Repetitive And Mild Traumatic Brain Injury, Christina H Acosta, Garrett A Clemons, Cristiane T Citadin, William C Carr, Mariana Sayuri Berto Udo, Vesna Tesic, Henry W Sanicola, Anne H Freelin, Jamie B Toms, J Dedrick Jordan, Bharat Guthikonda, Celeste Yin-Chieh Wu, Reggie Hui-Chao Lee, Hung Wen Lin

Faculty, Staff and Student Publications

Mild traumatic brain injury affects the largest proportion of individuals in the United States and world-wide. Pre-clinical studies of repetitive and mild traumatic brain injury (rmTBI) have been limited in their ability to recapitulate human pathology (i.e. diffuse rotational injury). We used the closed-head impact model of engineered rotation acceleration (CHIMERA) to simulate rotational injury observed in patients and to study the pathological outcomes post-rmTBI using C57BL/6J mice. Enhanced cytokine production was observed in both the cortex and hippocampus to suggest neuroinflammation. Furthermore, microglia were assessed via enhanced iba1 protein levels and morphological changes using immunofluorescence. In addition, LC/MS analyses …

A 3d Perfusable Platform For In Vitro Culture Of Patient Derived Xenografts, Lindsey K Sablatura, Kristin M Bircsak, Peter Shepherd, Madhavi Bathina, Karla Queiroz, Mary C Farach-Carson, Rick A Kittles, Pamela E Constantinou, Anthony Saleh, Nora M Navone, Daniel A Harrington

Faculty, Staff and Student Publications

Many advanced cancer models, such as patient-derived xenografts (PDXs), offer significant benefits in their preservation of the native tumor's heterogeneity and susceptibility to treatments, but face significant barriers to use in their reliance on a rodent host for propagation and screening. PDXs remain difficult to implement in vitro, particularly in configurations that enable both detailed cellular analysis and high-throughput screening (HTS). Complex multilineage co-cultures with stromal fibroblasts, endothelium, and other cellular and structural components of the tumor microenvironment (TME) further complicate ex vivo implementation. Herein, the culture of multiple prostate cancer (PCa)-derived PDX models as 3D clusters within engineered biomimetic …

Anaplastic Transformation In Thyroid Cancer Revealed By Single-Cell Transcriptomics, Lina Lu, Jennifer Rui Wang, Ying C Henderson, Shanshan Bai, Jie Yang, Min Hu, Cheng-Kai Shiau, Timothy Pan, Yuanqing Yan, Tuan M Tran, Jianzhuo Li, Rachel Kieser, Xiao Zhao, Jiping Wang, Roza Nurieva, Michelle D Williams, Maria E Cabanillas, Ramona Dadu, Naifa Lamki Busaidy, Mark Zafereo, Nicholas Navin, Stephen Y Lai, Ruli Gao

Faculty, Staff and Student Publications

The deadliest anaplastic thyroid cancer (ATC) often transforms from indolent differentiated thyroid cancer (DTC); however, the complex intratumor transformation process is poorly understood. We investigated an anaplastic transformation model by dissecting both cell lineage and cell fate transitions using single-cell transcriptomic and genetic alteration data from patients with different subtypes of thyroid cancer. The resulting spectrum of ATC transformation included stress-responsive DTC cells, inflammatory ATC cells (iATCs), and mitotic-defective ATC cells and extended all the way to mesenchymal ATC cells (mATCs). Furthermore, our analysis identified 2 important milestones: (a) a diploid stage, in which iATC cells were diploids with inflammatory …

Impact Of Cross-Ancestry Genetic Architecture On Gwass In Admixed Populations, Rachel Mester, Kangcheng Hou, Yi Ding, Gillian Meeks, Kathryn S Burch, Arjun Bhattacharya, Brenna M Henn, Bogdan Pasaniuc

Faculty, Staff and Student Publications

Genome-wide association studies (GWASs) have identified thousands of variants for disease risk. These studies have predominantly been conducted in individuals of European ancestries, which raises questions about their transferability to individuals of other ancestries. Of particular interest are admixed populations, usually defined as populations with recent ancestry from two or more continental sources. Admixed genomes contain segments of distinct ancestries that vary in composition across individuals in the population, allowing for the same allele to induce risk for disease on different ancestral backgrounds. This mosaicism raises unique challenges for GWASs in admixed populations, such as the need to correctly adjust …

Exploring Monitoring Strategies For Population Surveillance Of Hpv Vaccine Impact Using Primary Hpv Screening, Louiza S. Velentzis, David Hawkes, Michael Caruana, Julia Mi Brotherton, Megan A. Smith, Lara Roeske, Khurram A. Karim, Suzanne M. Garland, C David Wrede, Jeffery Tan, Cosette Wheeler, Philip E. Castle, Marion Saville, Karen Canfell

Pathology Research and Scholarship

Australia's cervical screening program transitioned from cytology to HPV-testing with genotyping for HPV16/18 in Dec'2017. We investigated whether program data could be used to monitor HPV vaccination program impact (commenced in 2007) on HPV16/18 prevalence and compared estimates with pre-vaccination benchmark prevalence. Pre-vaccination samples (2005-2008) (n = 1933; WHINURS), from 25 to 64-year-old women had been previously analysed with Linear Array (LA). Post-vaccination samples (2013-2014) (n = 2989; Compass pilot), from 25 to 64-year-old women, were analysed by cobas 4800 (cobas), and by LA for historical comparability. Age standardised pre-vaccination HPV16/18 prevalence was 4.85% (95%CI:3.81-5.89) by LA; post-vaccination estimates were …

Terrorist Attacks Against Sports Venues: Emerging Trends And Characteristics Spanning 50 Years, Grace R Rahman, Gregory N Jasani, Stephen Y Liang

2020-Current year OA Pubs

INTRODUCTION: Sports venues foster community and support local economies. Due to their capacity to host hundreds to thousands of spectators, sports venues are vulnerable to becoming targets of terrorism. Types of venues targeted, regional trends, and methods of attack employed world-wide have not been well-described.

METHODS: A search of the Global Terrorism Database (GTD) was conducted from 1970 through the end of 2019. Pre-coded variables for target type "business" and target subtype "entertainment/cultural/stadium/casino" were used to identify attacks involving venues where sports events might be viewed by spectators as part of an audience. Sports venues were specifically identified using the …

Replicative Acinetobacter Baumannii Strains Interfere With Phagosomal Maturation By Modulating The Vacuolar Ph, Jesus S. Distel, Gisela Di Venanzio, Joseph J. Mackel, David A. Rosen, Mario F. Feldman

2020-Current year OA Pubs

Bacterial pneumonia is a common infection of the lower respiratory tract that can afflict patients of all ages. Multidrug-resistant strains of Acinetobacter baumannii are increasingly responsible for causing nosocomial pneumonias, thus posing an urgent threat. Alveolar macrophages play a critical role in overcoming respiratory infections caused by this pathogen. Recently, we and others have shown that new clinical isolates of A. baumannii, but not the common lab strain ATCC 19606 (19606), can persist and replicate in macrophages within spacious vacuoles that we called Acinetobacter Containing Vacuoles (ACV). In this work, we demonstrate that the modern A. baumannii clinical isolate 398, …

Acinetobacter Baumannii Atcc 17978 Encodes A Microcin System With Antimicrobial Properties For Contact-Independent Competition, Fabiana Bisaro, Howard A Shuman, Mario F Feldman, Michael J Gebhardt, Stefan Pukatzki

2020-Current year OA Pubs

No abstract provided.

Protein Kinetics Of Superoxide Dismutase-1 In Familial And Sporadic Amyotrophic Lateral Sclerosis, Cindy V Ly, Margaret D Ireland, Wade K Self, James Bollinger, Jennifer Jockel-Balsarotti, Hillary Herzog, Peggy Allred, Leah Miller, Michael Doyle, Isabel Anez-Bruzual, Bhavesh Trikamji, Ted Hyman, Tyler Kung, Katherine Nicholson, Robert C Bucelli, Bruce W Patterson, Randall J Bateman, Timothy M Miller

2020-Current year OA Pubs

OBJECTIVE: Accumulation of misfolded superoxide dismutase-1 (SOD1) is a pathological hallmark of SOD1-related amyotrophic lateral sclerosis (ALS) and is observed in sporadic ALS where its role in pathogenesis is controversial. Understanding in vivo protein kinetics may clarify how SOD1 influences neurodegeneration and inform optimal dosing for therapies that lower SOD1 transcripts.

METHODS: We employed stable isotope labeling paired with mass spectrometry to evaluate in vivo protein kinetics and concentration of soluble SOD1 in cerebrospinal fluid (CSF) of SOD1 mutation carriers, sporadic ALS participants and controls. A deaminated SOD1 peptide, SDGPVKV, that correlates with protein stability was also measured.

RESULTS: In …

Contributions From Medical Geneticists In Clinical Trials Of Genetic Therapies: A Points To Consider Statement Of The American College Of Medical Genetics And Genomics (Acmg), Loren D M Peña, Lindsay C Burrage, Gregory M Enns, Edward D Esplin, Cary Harding, Jerry R Mendell, Zhiyv Neal Niu, Curt Scharfe, Timothy Yu, Dwight D Koeberl

Faculty, Staff and Students Publications

No abstract provided.

Differentially Expressed Tear Proteins In Sjögren's Syndrome Keratoconjunctivitis Sicca, Stephen P Yoon, Zhiyuan Yu, Stephen C Pflugfelder, Cintia S De Paiva

Faculty, Staff and Students Publications

Purpose: The purpose of this study was to determine if there are significant differences in the concentrations of tear proteins in Sjögren's syndrome keratoconjunctivitis sicca (SS KCS) compared to healthy controls.

Methods: Tear samples were collected with unmarked Schirmer strips from 15 patients with SS KCS and 21 healthy controls. Tear protein was eluted and the concentration measured. Inflammatory mediators were assayed with a Raybiotech L-507 glass slide array and normalized by strip wetting length. All patients underwent an ocular surface exam to evaluate tear break-up time (TBUT), corneal fluorescein (CF) staining, and conjunctival (CJ) staining. The symptom assessment questionnaire …

Examination Of Parent-Reported Differences In Children’S Daily Screen Use, Sleep, And Sleep Hygiene Behaviors During The School Year And Summer And Their Association With Bmi, Jennette P Moreno, Alexis C Wood, Brooke Reichek, Hafza Dadabhoy, Tom Baranowski, Debbe Thompson, Teresia M O'Connor

Faculty, Staff and Students Publications

OBJECTIVE: The current study examined school-summer differences in children's sleep patterns and sleep hygiene. Cross-sectional relationships with children's sleep, sleep hygiene, and weight status were explored during the school year and summer.

METHODS: Children (5-8 years) and their parents (n = 197 dyads) were recruited from 4 schools in southeastern Texas and via Facebook. Parents reported children's school year and summer sleep, sleep hygiene, and screen media use. Children's body mass index (BMI) was objectively assessed at the beginning and end of the summer. Associations between children's sleep hygiene and screen media use, sleep duration, and weight status were explored. …

Promoting Ocd Wellness And Resilience (Power) Study: Rationale, Design, And Methods, Jessica D Leuchter, Minjee Kook, Daniel A Geller, Alyssa G Hertz, Jessica Garcia, Erika S Trent, Tracey Dibbs, Ogechi Onyeka, Wayne K Goodman, Andrew G Guzick, Andrew D Wiese, Amanda D Palo, Brent J Small, H Blair Simpson, Lauren K Havel, Sohail A Nibras, Kirti Saxena, Eric A Storch

Faculty, Staff and Students Publications

Obsessive-compulsive disorder (OCD) affects 1-2% of children and is associated with functional impairment and diminished quality of life. Several treatments are efficacious: cognitive behavioral therapy (CBT) with exposure and response prevention, serotonin reuptake inhibitor (SRI) monotherapy, and combined treatment (SRI + CBT). Expert clinician-informed practice parameters suggest that youth with mild to moderate OCD should be treated initially with CBT yet SRIs are frequently employed as the first-line intervention or in combination with psychotherapy in applied practice. Empirical data to guide SRI discontinuation in pediatric OCD are very limited. This study, Promoting OCD Wellness and Resiliency (POWER), aims to address …

Defining Myocardial Infarction In Trials Of People Receiving Hemodialysis: Consensus Report From The Song-Hd Mi Expert Working Group, Emma O'Lone, Fred S Apple, James O Burton, Fergus J Caskey, Jonathan C Craig, Christopher R Defilippi, Derek Forfang, Karen A Hicks, Vivekanand Jha, Kenneth W Mahaffey, Patrick B Mark, Patrick Rossignol, Nicole Scholes-Robertson, Allison Jaure, Andrea K Viecelli, Angela Y Wang, David C Wheeler, David White, Wolfgang C Winkelmayer, Charles A Herzog

Faculty, Staff and Students Publications

Cardiovascular disease is the leading cause of death in patients receiving hemodialysis. Currently, there is no standardized definition of myocardial infarction (MI) for patients receiving hemodialysis. Through an international consensus process MI was established as the core CVD measure for this population in clinical trials. The Standardised Outcomes in Nephrology Group-Hemodialysis (SONG-HD) initiative convened a multidisciplinary, international working group to address the definition of MI in this population. On the basis of current evidence, the working group recommends using the Fourth Universal Definition of Myocardial Infarction with specific caveats with regard to the interpretation of "ischemic symptoms" and performing a …

Race-Free Estimated Glomerular Filtration Rate Equation In Kidney Transplant Recipients: Development And Validation Study, Marc Raynaud, Solaf Al-Awadhi, Ivana Juric, Gillian Divard, Yannis Lombardi, Nikolina Basic-Jukic, Olivier Aubert, Laurence Dubourg, Ingrid Masson, Christophe Mariat, Dominique Prié, Vincent Pernin, Moglie Le Quintrec, Timothy S Larson, Mark D Stegall, Boris Bikbov, Piero Ruggenenti, Laurent Mesnard, Hassan N Ibrahim, Marie Bodilsen Nielsen, Arthur J Matas, Brian J Nankivell, Stan Benjamens, Robert A Pol, Stephan J L Bakker, Xavier Jouven, Christophe Legendre, Nassim Kamar, Byron H Smith, Hani M Wadei, Antoine Durrbach, Flavio Vincenti, Giuseppe Remuzzi, Carmen Lefaucheur, Andrew J Bentall, Alexandre Loupy

Faculty, Staff and Student Publications

OBJECTIVE: To compare the performance of a newly developed race-free kidney recipient specific glomerular filtration rate (GFR) equation with the three current main equations for measuring GFR in kidney transplant recipients.

DESIGN: Development and validation study SETTING: 17 cohorts in Europe, the United States, and Australia (14 transplant centres, three clinical trials).

PARTICIPANTS: 15 489 adults (3622 in development cohort (Necker, Saint Louis, and Toulouse hospitals, France), 11 867 in multiple external validation cohorts) who received kidney transplants between 1 January 2000 and 1 January 2021.

MAIN OUTCOME MEASURE: The main outcome measure was GFR, measured according to local practice. …

Dissociation Protocols Used For Sarcoma Tissues Bias The Transcriptome Observed In Single-Cell And Single-Nucleus Rna Sequencing, Danh D Truong, Salah-Eddine Lamhamedi-Cherradi, Robert W Porter, Sandhya Krishnan, Jyothishmathi Swaminathan, Amber Gibson, Alexander J Lazar, J Andrew Livingston, Vidya Gopalakrishnan, Nancy Gordon, Najat C Daw, Nicholas E Navin, Richard Gorlick, Joseph A Ludwig

Faculty, Staff and Student Publications

BACKGROUND: Single-cell RNA-seq has emerged as an innovative technology used to study complex tissues and characterize cell types, states, and lineages at a single-cell level. Classification of bulk tumors by their individual cellular constituents has also created new opportunities to generate single-cell atlases for many organs, cancers, and developmental models. Despite the tremendous promise of this technology, recent evidence studying epithelial tissues and diverse carcinomas suggests the methods used for tissue processing, cell disaggregation, and preservation can significantly bias gene expression and alter the observed cell types. To determine whether sarcomas - tumors of mesenchymal origin - are subject to …

Leukemia Relapse Via Genetic Immune Escape After Allogeneic Hematopoietic Cell Transplantation, Simona Pagliuca, Francesca Ferraro, Et Al.

2020-Current year OA Pubs

Graft-versus-leukemia (GvL) reactions are responsible for the effectiveness of allogeneic hematopoietic cell transplantation as a treatment modality for myeloid neoplasia, whereby donor T- effector cells recognize leukemia neoantigens. However, a substantial fraction of patients experiences relapses because of the failure of the immunological responses to control leukemic outgrowth. Here, through a broad immunogenetic study, we demonstrate that germline and somatic reduction of human leucocyte antigen (HLA) heterogeneity enhances the risk of leukemic recurrence. We show that preexistent germline-encoded low evolutionary divergence of class II HLA genotypes constitutes an independent factor associated with disease relapse and that acquisition of clonal somatic …

Glial Progenitor Heterogeneity And Key Regulators Revealed By Single-Cell Rna Sequencing Provide Insight To Regeneration In Spinal Cord Injury, Haichao Wei, Xizi Wu, Joseph Withrow, Raquel Cuevas-Diaz Duran, Simranjit Singh, Lesley S Chaboub, Jyotirmoy Rakshit, Julio Mejia, Andrew Rolfe, Juan J Herrera, Philip J Horner, Jia Qian Wu

Faculty, Staff and Student Publications

Recent studies have revealed the heterogeneous nature of astrocytes; however, how diverse constituents of astrocyte-lineage cells are regulated in adult spinal cord after injury and contribute to regeneration remains elusive. We perform single-cell RNA sequencing of GFAP-expressing cells from sub-chronic spinal cord injury models and identify and compare with the subpopulations in acute-stage data. We find subpopulations with distinct functional enrichment and their identities defined by subpopulation-specific transcription factors and regulons. Immunohistochemistry, RNAscope experiments, and quantification by stereology verify the molecular signature, location, and morphology of potential resident neural progenitors or neural stem cells in the adult spinal cord before …

Discovery Of Phosphorylated Lantibiotics With Proimmune Activity That Regulate The Oral Microbiome, Abdelahhad Barbour, Leif Smith, Morvarid Oveisi, Mckinley Williams, Ruo Chen Huang, Cara Marks, Noah Fine, Chunxiang Sun, Fereshteh Younesi, Sina Zargaran, Ravi Orugunty, Thomas D Horvath, Sigmund J Haidacher, Anthony M Haag, Amarpreet Sabharwal, Boris Hinz, Michael Glogauer

Faculty, Staff and Students Publications

Lantibiotics are ribosomally synthesized and posttranslationally modified peptides (RiPPs) that are produced by bacteria. Interest in this group of natural products is increasing rapidly as alternatives to conventional antibiotics. Some human microbiome–derived commensals produce lantibiotics to impair pathogens’ colonization and promote healthy microbiomes. Streptococcus salivarius is one of the first commensal microbes to colonize the human oral cavity and gastrointestinal tract, and its biosynthesis of RiPPs, called salivaricins, has been shown to inhibit the growth of oral pathogens. Herein, we report on a phosphorylated class of three related RiPPs, collectively referred to as salivaricin 10, that exhibit proimmune activity and …

Direct Haplotype-Resolved 5-Base Hifi Sequencing For Genome-Wide Profiling Of Hypermethylation Outliers In A Rare Disease Cohort., Warren A. Cheung, Adam F. Johnson, William J. Rowell, Emily G. Farrow, Richard Hall, Ana S A Cohen, John C. Means, Tricia N. Zion, Daniel M. Portik, Christopher T. Saunders, Boryana Koseva, Chengpeng Bi, Tina K. Truong, Carl F. Schreck, Byunggil Yoo, Jeffrey J. Johnston, Margaret Gibson, Gilad Evrony, William B. Rizzo, Isabelle Thiffault, Scott T. Younger, Tom Curran, Aaron M. Wenger, Elin Grundberg, T Pastinen

Manuscripts, Articles, Book Chapters and Other Papers

Long-read HiFi genome sequencing allows for accurate detection and direct phasing of single nucleotide variants, indels, and structural variants. Recent algorithmic development enables simultaneous detection of CpG methylation for analysis of regulatory element activity directly in HiFi reads. We present a comprehensive haplotype resolved 5-base HiFi genome sequencing dataset from a rare disease cohort of 276 samples in 152 families to identify rare (~0.5%) hypermethylation events. We find that 80% of these events are allele-specific and predicted to cause loss of regulatory element activity. We demonstrate heritability of extreme hypermethylation including rare cis variants associated with short (~200 bp) and …

Differential Gene Expression Of Fresh Tissue And Patient-Derived Explants’ Matricellular Proteins Augment Inflammatory Breast Cancer Metastasis: The Possible Role Of Il-6 And Mcp-1, Alshaimaa Tarek, Hossam Taha Mohamed, Aya Ali El-Sharkawy, Shrouk Khalaf El-Sayed, Jon Mark Hirshon, Wendy A Woodward, Mohamed El-Shinawi, Mona Mostafa Mohamed

Faculty, Staff and Student Publications

BACKGROUND: Matricellular proteins comprising matrisome and adhesome are responsible for structure integrity and interactions between cells in the tumour microenvironment of breast cancer. Changes in the gene expression of matrisome and adhesome augment metastasis. Since inflammatory breast cancer (IBC) is characterized by high metastatic behaviour. Herein, we compared the gene expression profile of matrisome and adhesome in non-IBC and IBC in fresh tissue and ex vivo patient-derived explants (PDEs) and we also compared the secretory inflammatory mediators of PDEs in non-IBC and IBC to identify secretory cytokines participate in cross-talk between cells via interactions with matrisome and adhisome.

METHODS: Fifty …

Upregulation Of The Oct3/4 Network In Basal Breast Cancer Is Associated With Its Metastatic Potential And Shows Tissue Dependent Variability, Robin G Rajan, Raisa I Krutilina, Tatyana N Ignatova, Zoran S Pavicevich, Galina M Dulatova, Maria A Lane, Arindam R Chatterjee, Robert J Rooney, Mymoon Antony, Vivian R Hagerty, Nickolay V Kukekov, Khalid A Hanafy, Frank D Vrionis

2020-Current year OA Pubs

Adaptive plasticity of Breast Cancer stem cells (BCSCs) is strongly correlated with cancer progression and resistance, leading to a poor prognosis. In this study, we report the expression profile of several pioneer transcription factors of the

A Single-Cell Multiomic Analysis Of Kidney Organoid Differentiation, Yasuhiro Yoshimura, Yoshiharu Muto, Nicolas Ledru, Haojia Wu, Kohei Omachi, Jeffrey H Miner, Benjamin D Humphreys

2020-Current year OA Pubs

Kidney organoids differentiated from pluripotent stem cells are powerful models of kidney development and disease but are characterized by cell immaturity and off-target cell fates. Comparing the cell-specific gene regulatory landscape during organoid differentiation with human adult kidney can serve to benchmark progress in differentiation at the epigenome and transcriptome level for individual organoid cell types. Using single-cell multiome and histone modification analysis, we report more broadly open chromatin in organoid cell types compared to the human adult kidney. We infer enhancer dynamics by cis-coaccessibility analysis and validate an enhancer driving transcription of